Shikonin Suppresses Cell Tumorigenesis in Gastric Cancer Associated with the Inhibition of c-Myc and Yap-1

Abstract

aims: To explore the potential roles and mechanisms of shikonin in gastric cancer by network pharmacology and biological experiments. background: Gastric cancer is one of the most common and deadly cancers in the world. Although the survival rate of gastric cancer has improved worldwide for many years, it is difficult to treat due to its high tumor recurrence and easy resistance to chemotherapeutic drugs.Recently studies showed that traditional Chinese medicine Shikonin had anti-cancer effects with their unique advantages of high efficiency and small side effect. objective: To study the potential roles and mechanisms of shikonin in gastric cancer by network pharmacology and biological experiments. method: The key genes and targets of shikonin in gastric cancer were predicted by network pharmacology and molecular docking study. The effect of shikonin on the proliferation, migration and invasion of gastric cancer cells was detected by the CCK8 method, Wound healing and Transwell assays. The expression levels of c-Myc and Yap-1 protein in gastric cancer cells after shikonin intervention were detected by western blotting. result: The study of network pharmacology found that the key target genes of shikonin on gastric cancer cells were c-Myc, Yap-1, AKT1,etc. GO and KEGG analysis showed regulation of cell migration, proliferation, adhesion and other biological processes; PI3K-Akt signaling pathway, HIF-1 signaling pathway, necroptosis and other cancer pathways. Molecular docking showed that shikonin was most closely combined with protooncogene c-Myc and Yap-1. In vitro experiments showed that the proliferation rate, migration and invasion ability of gastric cancer cell group decreased significantly after shikonin intervention for 24h, and it was concentration-dependent. The expression levels of c-Myc and Yap-1 in gastric cancer cells were significantly decreased after shikonin intervention. conclusion: This study showed that protooncogene c-Myc and Yap-1 were the core target genes of shikonin on gastric cancer cells. Shikonin may suppress gastric cancer cells by inhibiting the protooncogene c-Myc and Yap-1. It suggested shikonin maybe a good candidate for the treatment of gastric cancer.